Is ANK2 p.Ala467= (c.1401A>G) pathogenic?

ANK2 p.Ala467= (c.1401A>G) is classified Benign/Likely benign in ANK2 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-05-01). Low-frequency (popmax 1.37%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ANK2 p.Ala467= (c.1401A>G)?

ANK2 p.Ala467= (c.1401A>G) is associated with Cardiovascular phenotype, long QT syndrome, cardiac arrhythmia, ankyrin-B-related (ClinVar).

How common is ANK2 p.Ala467= (c.1401A>G) in the general population?

ANK2 p.Ala467= (c.1401A>G) is low-frequency (popmax 1.37%, mid) (gnomAD).

ANK2 p.Ala467=

c.1401A>G · rs142159132 · VCV238570

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.37%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -4.9
Overall
CADD	3.235	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.37% Middle Eastern · 82/6,004 alleles

Filtering AF 1.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.327% 5,125/1,565,198 alleles · low-frequency exomes 4,721/1,412,888 · genomes 404/152,310 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.37%	73
Ashkenazi Jewishnot grpmax-eligible	0.923%	108
European (non-Finnish)	0.377%	265
Remaining individualsnot grpmax-eligible	0.33%	303
Admixed American	0.254%	393
African / African-American	0.0621%	1,611
South Asian	0.0436%	2,294
Finnishnot grpmax-eligible	0.0181%	5,533

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANK2
Protein: p.Ala467=
Coding: c.1401A>G
MANE Select: NM_001148
dbSNP: rs142159132
Type: single nucleotide variant
Location: chr4:113264911 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 467: an α-helix

Full ANK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: long QT syndrome cardiac arrhythmia, ankyrin-B-related

Similar variants

ANK2 p.Ala467Ser Uncertain significance ★★ same residue
ANK2 p.Ala467Val Uncertain significance ★ same residue
ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg1088Ter Pathogenic ★★ same condition
ANK2 p.Arg3113Ter Pathogenic ★★ same condition
ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
ANK2 p.Arg977Ter Pathogenic ★★ same condition
ANK2 c.11032+11G>T Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ank2-p-ala467 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown